Clinicomicrobiological risk factors for infective endocarditis in viridans group streptococci bacteraemia.

BACKGROUND: When to perform echocardiography to rule out infective endocarditis (IE) in patients with viridans group streptococci (VGS) bloodstream infections (BSIs) is unclear. OBJECTIVES: We aimed to identify independent risk factors for IE in patients with VGS BSI. METHODS: This retrospective study conducted at Seoul National University Hospital from January 2013 to December 2022 involved patients with VGS and nutritionally variant streptococcal BSI, excluding single positive blood cultures and polymicrobial BSI cases. Independent risk factors were identified by multivariate logistic regression and sensitivity analyses according to echocardiography results, VGS species or the inclusion of possible IE cases. RESULTS: Of 845 VGS BSI cases, 349 were analysed and 86 IE cases were identified (24.6%). In the multivariate analysis, heart valve disease [adjusted odds ratio (aOR), 14.14, 95% CI, 6.14-32.58; P < 0.001], persistent bacteraemia (aOR, 5.12, 95% CI, 2.03-12.94; P = 0.001), age (per year, aOR, 0.98; 95% CI, 0.96-1.00; P = 0.015), solid cancer (aOR, 0.26; 95% CI, 0.13-0.53; P < 0.001) and haematologic malignancy (aOR, 0.04; 95% CI, 0.01-0.41; P = 0.006) were independently associated with IE. Sensitivity analyses yielded consistent results; also, infection by a member of the mitis group was independent risk factor for IE (aOR, 6.50; 95% CI, 2.87-14.68; P < 0.001). CONCLUSIONS: Younger age, heart valve disease, persistent bacteraemia, absence of underlying malignancy and BSI by a member of the mitis group were independent risk factors for IE in patients with VGS BSI. Echocardiographic evaluation could be prudently considered based on these clinicomicrobiological risk factors.

Pre-Clinical Studies of a Novel Bispecific Fusion Protein Targeting C3b and VEGF in Neovascular and Nonexudative AMD Models.

INTRODUCTION: KNP-301 is a bi-specific fragment crystallizable region (Fc) fusion protein, which inhibits both C3b and vascular endothelial growth factor (VEGF) simultaneously for patients with late-stage age-related macular degeneration (AMD). The present study evaluated in vitro potency, in vivo efficacy, intravitreal pharmacokinetics (IVT PK), and injectability of KNP-301. METHODS: C3b and VEGF binding of KNP-301 were assessed by surface plasmon resonance (SPR) and enzyme-linked immunosorbent assay (ELISA), and cellular bioassays. A laser-induced choroidal neovascularization (CNV) model and a sodium iodate-induced nonexudative AMD model were used to test the in vivo efficacy of mouse surrogate of KNP-301. Utilizing fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) scans, the reduction in disease lesions were analyzed in a CNV mouse model. In the nonexudative AMD mouse model, outer nuclear layer (ONL) was assessed by immunofluorescence staining. Lastly, intravitreal pharmacokinetic study was conducted with New Zealand white rabbits via IVT administration of KNP-301 and injectability of KNP-301 was examined by a viscosity test at high concentrations. RESULTS: KNP-301 bound C3b selectively, which resulted in a blockade of the alternative pathway, not the classical pathway. KNP-301 also acted as a VEGF trap, impeding VEGF-mediate signaling. Our dual-blockade strategy was effective in both neovascular and nonexudative AMD models. Moreover, KNP-301 had an advantage of potentially less frequent dosing due to the long half-life in the intravitreal chamber. Our viscosity assessment confirmed that KNP-301 meets the criteria of the IVT injection. CONCLUSIONS: Unlike current therapies, KNP-301 is expected to cover patients with late-stage AMD of both neovascular and nonexudative AMD, and its long-term PK profile at the intravitreal chamber would allow convenience in the dosing interval of patients.

Impact of medical waste bin on contamination of patient's environment: An experimental study.

BACKGROUND: Medical waste bins are a potential source of microbial contamination in the hospital environment, while there is no clear guidance for the management of them. We aimed to assess the impact of medical waste bins on patient's environment. METHODS: This experimental study simulated microbial contamination by performing medical procedures on a patient model with fluorescent lotion. The waste bin was set as initially empty or two-thirds filled with waste, open or with a lid. The percentage of fluorescent-contaminated area in designated patient's environments was analyzed by 2 independent observers. RESULTS: Among a total of 120 experiments, the sides of the bins were more contaminated in open-occupied bins compared to open-empty bins and in open-occupied bins compared to lid-occupied bins (median 1.9175% vs 0.0916% [P = .001] and 1.9175% vs 0.0899% [P = .003], respectively). The top of the bedside equipment trolley for preparing medical procedures was more contaminated in lid-occupied bins than open-occupied bins (median 0.0080% vs 0.0040%, P = .013). DISCUSSION: In addition to reducing contamination of the bin itself, the manually operated lid had a potential risk of contributing to microbial transmission by contaminating the equipment trolley. CONCLUSIONS: Medical waste bins should be kept no more than two-thirds full, and caution should be taken when using the manually operated lid, to avoid cross-contamination.

The Beneficial Roles of Sargassum spp. in Skin Disorders.

As the body's largest organ, the skin is located at the internal and external environment interface, serving as a line of defense against various harmful stressors. Recently, marine-derived physiologically active ingredients have attracted considerable attention in the cosmeceutical industry due to their beneficial effects on skin health. Sargassum, a genus of brown macroalgae, has traditionally been consumed as food and medicine in several countries and is rich in bioactive compounds such as meroterpenoids, sulfated polysaccharides, fucoidan, fucoxanthin, flavonoids, and terpenoids. Sargassum spp. have various beneficial effects on skin disorders. They help with atopic dermatitis by improving skin barrier protection and reducing inflammation. Several species show potential in treating acne by inhibiting bacterial growth and reducing inflammation. Some species, such as Sargassum horneri, demonstrate antiallergic effects by modulating mast cell activity. Certain Sargassum species exhibit anticancer activity by inhibiting tumor growth and promoting apoptosis, and some species help with wound healing by promoting angiogenesis and reducing oxidative stress. Overall, Sargassum spp. demonstrate potential for treating and managing various skin conditions. Therefore, the bioactive compounds of Sargassum spp. may be natural ingredients with a wide range of functional properties for preventing and treating skin disorders. The present review focused on the various biological effects of Sargassum extracts and derived compounds on skin disorders.

Risk factors for resistant gram-positive bacteremia in febrile neutropenic patients with cancer.

BACKGROUND: Gram-positive bacteria are frequently resistant to empirical beta-lactams in febrile neutropenic patients with cancer. As microbiology and antibiotic susceptibility changes, we reevaluated the risk factors for resistant Gram-positive bacteremia in febrile neutropenic patients with cancer. METHODS: Episodes of bacteremic febrile neutropenia in Seoul National University Hospital from July 2019 to June 2022 were reviewed. Resistant Gram-positive bacteria were defined as a pathogen susceptible only to glycopeptide or linezolid in vitro (e.g., methicillin-resistant staphylococci, penicillin-resistant viridans streptococci, and ampicillin-resistant enterococci). Episodes were compared to identify independent risk factors for resistant Gram-positive bacteremia. RESULTS: Of 225 episodes, 78 (34.7%) involved resistant Gram-positive bacteremia. Multivariate analysis revealed that breakthrough bacteremia while being administered antibiotics (adjusted odds ratio [aOR], 6.794; 95% confidence interval [95% CI], 3.130-14.749; P < 0.001) and catheter-related infection (aOR 4.039, 95% CI 1.366-11.946; P = 0.012) were associated with resistant Gram-positive bacteremia. Chronic liver disease (aOR 0.231, 95% CI 0.059-0.905; P = 0.035) and hypotension at bacteremia (aOR 0.454, 95% CI 0.218-0.945; P = 0.035) were inversely associated with resistant Gram-positive bacteremia. CONCLUSIONS: Resistant Gram-positive bacteria should be considered in breakthrough bacteremia and catheter-related infection in febrile neutropenic patients with cancer.

Staphylococcus argenteus bacteremia in the Republic of Korea.

In 2015, Staphylococcus argenteus and Staphylococcus schweitzeri were proposed as new species, distinct from Staphylococcus aureus and collectively referred to as the S. aureus complex. However, no clinical reports of these new species exist in Korea. Upon the application of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for all bloodstream isolates since September 2022, S. argenteus was identified in one patient. Therefore, we aimed to search for new species among the archives of the S. aureus bacteremia cohort and describe their clinical and microbiological characteristics. Among the 691 archived S. aureus isolates between 2012 and 2018, one was identified as S. argenteus via MALDI-TOF MS. Both S. argenteus isolates (one in 2022) were obtained from patients with extensive pneumonia accompanied by bacteremia and both cases had fatal outcomes. They harbored multiple virulence genes (clfA, clfB, fnbpA, sdrC, sdrD, sdrE, bbp, cna, see, seg, sei, blaZ, fnbpB, and map) but did not harbor mecA and pvl. No matched sequence type (ST) was found in either isolate, and both S. argenteus isolates were closely related to ST1594, ST1593, ST1793, and ST1303, which belonged to S. argenteus. S. argenteus accounted for <1% of the S. aureus complex but had clinical characteristics similar to S. aureus. Therefore, clinicians should be aware of these factors to avoid misidentifying these strains as coagulase-negative staphylococci, and appropriate reporting is required to minimize confusion.IMPORTANCEStaphylococcus argenteus, a member of Staphylococcus aureus complex, has been reported as an important pathogen that causes clinically invasive infections in humans similar to S. aureus. Clinical isolates of S. argenteus have been reported across the world, showing a large geographical difference in prevalence and genomic profile. However, there have been no clinical reports regarding this new species in Korea. This is the first report to investigate the clinical and genetic characteristics of S. argenteus identified in patients with bacteremia, and the proportion of S. argenteus bacteremia among S. aureus bacteremia cohort in Korea.

Sargachromenol Attenuates Inflammatory Responses by Regulating NF-κB and Nrf2 Pathways in RAW 264.7 Cells and LPS-treated Mice.

This study aims to explore the anti-inflammatory mechanisms of sargachromenol in both RAW 264.7 cells and lipopolysaccharide (LPS)-treated mice, as previous reports have suggested that sargachromenol possesses anti-aging, anti-inflammatory, antioxidant, and neuroprotective properties. Although the precise mechanism behind its anti-inflammatory activity remains unclear, pretreatment with sargachromenol effectively reduced the production of nitric oxide, prostaglandin E2, and interleukin (IL)-1ß in LPS-stimulated RAW 264.7 cells by inhibiting cyclooxygenase-2. Moreover, sargachromenol inhibited the activation of nuclear factor-κB (NF-κB) by preventing the degradation of the inhibitor of κB-α (IκB-α) and inhibiting protein kinase B (Akt) phosphorylation in LPS-stimulated cells. We also found that sargachromenol induced the production of heme oxygenase-1 (HO-1) by activating the nuclear transcription factor erythroid-2-related factor 2 (Nrf2). In LPS-treated mice, oral administration of sargachromenol effectively reduced the levels of IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α) in the serum, suggesting its ability to suppress the production of inflammatory mediators by inhibiting the Akt/NF-κB pathway and upregulating the Nrf2/HO-1 pathway.

LPS-Induced Modifications in Macrophage Transcript and Secretion Profiles Are Linked to Muscle Wasting and Glucose Intolerance.

Macrophages are versatile immune cells that play crucial roles in tissue repair, immune defense, and the regulation of immune responses. In the context of skeletal muscle, they are vital for maintaining muscle homeostasis but macrophage-induced chronic inflammation can lead to muscle dysfunction, resulting in skeletal muscle atrophy characterized by reduced muscle mass and impaired insulin regulation and glucose uptake. Although the involvement of macrophage-secreted factors in inflammation-induced muscle atrophy is well-established, the precise intracellular signaling pathways and secretion factors affecting skeletal muscle homeostasis require further investigation. This study aimed to explore the regulation of macrophage-secreted factors and their impact on muscle atrophy and glucose metabolism. By employing RNA sequencing (RNA-seq) and proteome array, we uncovered that factors secreted by lipopolysaccharide (LPS)-stimulated macrophages upregulated markers of muscle atrophy and pro-inflammatory cytokines, while concurrently reducing glucose uptake in muscle cells. The RNA-seq analysis identified alterations in gene expression patterns associated with immune system pathways and nutrient metabolism. The utilization of gene ontology (GO) analysis and proteome array with macrophage-conditioned media revealed the involvement of macrophage-secreted cytokines and chemokines associated with muscle atrophy. These findings offer valuable insights into the regulatory mechanisms of macrophage-secreted factors and their contributions to muscle-related diseases.

Possibility of Decreasing Incidence of Human Immunodeficiency Virus Infection in Korea.

BACKGROUND: The number of newly diagnosed cases of human immunodeficiency virus (HIV) infection in Korea, which had increased until 2019, has markedly decreased since the coronavirus disease 2019 pandemic started. This study evaluated whether the decrease is due to a reduction in the incidence of HIV infection and/or delayed diagnosis during the pandemic. MATERIALS AND METHODS: We reviewed the medical records of 587 newly diagnosed patients with HIV infection between February 2018 and January 2022 from four general hospitals, and their characteristics were compared between the pre-pandemic and pandemic periods. The lapse time from infection to diagnosis was estimated using an HIV modeling tool. RESULTS: The estimated mean times to diagnosis were 5.68 years (95% confidence interval [CI]: 4.45 - 6.51 years) and 5.41 years (95% CI: 4.09 - 7.03 years) before and during the pandemic, respectively (P = 0.016). The proportion of patients with acquired immunodeficiency syndrome-defining illnesses, expected to visit hospitals regardless of the pandemic, decreased from 17.2% before the pandemic to 11.9% during the pandemic (P = 0.086). CONCLUSION: The decrease in the number of newly diagnosed cases of HIV infection in Korea might have resulted from an actual decrease in the incidence of HIV infection rather than a worsening of underdiagnosis or delayed diagnosis.

The Role of Macrophage Populations in Skeletal Muscle Insulin Sensitivity: Current Understanding and Implications.

Insulin resistance is a crucial factor in the development of type 2 diabetes mellitus (T2DM) and other metabolic disorders. Skeletal muscle, the body's largest insulin-responsive tissue, plays a significant role in the pathogenesis of T2DM due to defects in insulin signaling. Recently, there has been growing evidence that macrophages, immune cells essential for tissue homeostasis and injury response, also contribute to the development of skeletal muscle insulin resistance. This review aims to summarize the current understanding of the role of macrophages in skeletal muscle insulin resistance. Firstly, it provides an overview of the different macrophage populations present in skeletal muscle and their specific functions in the development of insulin resistance. Secondly, it examines the underlying mechanisms by which macrophages promote or alleviate insulin resistance in skeletal muscle, including inflammation, oxidative stress, and altered metabolism. Lastly, the review discusses potential therapeutic strategies targeting macrophages to improve skeletal muscle insulin sensitivity and metabolic health.

SMP30-mediated synthesis of vitamin C activates the liver PPARα/FGF21 axis to regulate thermogenesis in mice.

The vitamin-C-synthesizing enzyme senescent marker protein 30 (SMP30) is a cold resistance gene in Drosophila, and vitamin C concentration increases in brown adipose tissue post-cold exposure. However, the roles of SMP30 in thermogenesis are unknown. Here, we tested the molecular mechanism of thermogenesis using wild-type (WT) and vitamin C-deficient SMP30-knockout (KO) mice. SMP30-KO mice gained more weight than WT mice without a change in food intake in response to short-term high-fat diet feeding. Indirect calorimetry and cold-challenge experiments indicated that energy expenditure is lower in SMP30-KO mice, which is associated with decreased thermogenesis in adipose tissues. Therefore, SMP30-KO mice do not lose weight during cold exposure, whereas WT mice lose weight markedly. Mechanistically, the levels of serum FGF21 were notably lower in SMP30-KO mice, and vitamin C supplementation in SMP30-KO mice recovered FGF21 expression and thermogenesis, with a marked reduction in body weight during cold exposure. Further experiments revealed that vitamin C activates PPARα to upregulate FGF21. Our findings demonstrate that SMP30-mediated synthesis of vitamin C activates the PPARα/FGF21 axis, contributing to the maintenance of thermogenesis in mice.

Potential Beneficial Effects of Sargassum spp. in Skin Aging.

Seaweeds are receiving much attention as a rich source of bioactive compounds with cosmeceutical potential. Recent studies have revealed that Sargassum spp., a genus of brown algae in the family Sargassaceae, has multiple functions in preventing and improving skin aging. Sargassum spp. contains many bioactive compounds, such as fucoidan, fucoxanthin, terpenoids, flavonoids, and meroterpenoids. These Sargassum spp. extracts and derivative compounds have excellent potential for skincare, as they exhibit skin health-promoting properties, including antioxidants, anti-inflammation, whitening, skin barrier repair, and moisturizing. Therefore, searching for bioactive compounds in marine resources such as Sargassum spp. could be an attractive approach to preventing and improving skin aging. The current review focused on the various biological abilities of Sargassum extracts or derived compounds for anti-skin aging.

Metabolic Diseases and Risk of Head and Neck Cancer: A Cohort Study Analyzing Nationwide Population-Based Data.

The aim of the study was to investigate the association between metabolic diseases and the risk of head and neck cancer (HNC) using nationwide population-based big data. This retrospective cohort study was conducted using the Korean National Health Insurance Service health checkup database. A total of 4,575,818 participants aged >40 years who received a health checkup in 2008 were enrolled, and we studied the incidence of HNC until 2019. We analyzed the risk of HNC according to the presence of metabolic diseases, such as obesity, dyslipidemia, hypertension, and diabetes. Although metabolic syndrome itself was not associated with HNC, each component of metabolic syndrome was associated with HNC. Underweight and diabetes were risk factors for HNC (HR: 1.694). High total cholesterol and high low-density lipoprotein cholesterol levels were factors that decreased the risk (HR 0.910 and 0.839). When we analyzed men and women separately, low total cholesterol level, low low-density lipoprotein cholesterol level, and hypertension were risk factors only in men. In addition, pre-obesity, obesity, and central obesity decreased the risk only in men. Each metabolic disease affects HNC in different ways. Underweight and diabetes increased the risk of HNC, whereas high total cholesterol and high low-density lipoprotein cholesterol levels decreased the risk of HNC.

Maclurin Exhibits Antioxidant and Anti-Tyrosinase Activities, Suppressing Melanogenesis.

Maclurin is rich in some edible fruits such as Morus alba (white mulberry) and Garcinia mangostana. Although maclurin showed anti-cancer and antioxidant effects, its roles in ultraviolet (UV)-induced melanogenesis have not been studied. Here, we investigated the effects of maclurin in melanogenesis using skin cells and a three-dimensional human skin model. When the cytotoxicity of maclurin was examined in B16F10 cells, no cytotoxicity was found up to 20 µM. Maclurin suppressed UVB-mediated tyrosinase activation and melanin accumulation in B16F10 cells without changes in mRNA levels of melanogenesis-related genes including tyrosinase, TRP1, TRP2, CREB, and MITF. Moreover, maclurin reduced melanin contents in melan-a cells, a cell line for normal melanocytes. When applied to a human skin model consisting of the epidermis and melanocytes, maclurin significantly reduced UVB-induced melanin accumulation (~47%) in a concentration-dependent manner based on microscopic observation and Fontana-Masson staining. Protein-ligand docking simulation followed by binding residue analysis showed that maclurin may bind to inactivate tyrosinase by forming multiple hydrogen bonds and hydrophobic and aromatic interactions with the residues of tyrosinase. Together, our study suggests that maclurin may be applied as an anti-melanogenic agent.

Nutrients against Glucocorticoid-Induced Muscle Atrophy.

Glucocorticoid excess is a critical factor contributing to muscle atrophy. Both endogenous and exogenous glucocorticoids negatively affect the preservation of muscle mass and function. To date, the most effective intervention to prevent muscle atrophy is to apply a mechanical load in the form of resistance exercise. However, glucocorticoid-induced skeletal muscle atrophy easily causes fatigue in daily physical activities, such as climbing stairs and walking at a brisk pace, and reduces body movements to cause a decreased ability to perform physical activity. Therefore, providing adequate nutrients in these circumstances is a key factor in limiting muscle wasting and improving muscle mass recovery. The present review will provide an up-to-date review of the effects of various nutrients, including amino acids such as branched-chain amino acids (BCAAs) and ß-hydroxy ß-methylbutyrate (HMB), fatty acids such as omega-3, and vitamins and their derivates on the prevention and improvement of glucocorticoid-induced muscle atrophy.

Galla rhois water extract inhibits enzymatic browning in apple juice partly by binding to and inactivating polyphenol oxidase.

Although Galla rhois has been used as a traditional medicine in Asian countries, there was no application of it in anti-browning food additives. Here, we tested whether Galla rhois inhibits apple juice browning. Apple juice browning was blocked at 250-1000 µg/ml of Galla rhois for 16 days but the effect of vitamin C did not last until a day. In vitro assays showed that the antioxidant capacity of Galla rhois was stronger than that of vitamin C. Further analysis by UPLC-MS/MS identified 17 phytochemicals containing gallotannin derivatives. Docking simulation and polyphenol oxidase activity assay indicate that the mechanisms underlying Galla rhois-mediated inhibition of the enzymatic browning include but are not limited to the combined effects of multiple compounds including galloylglucose- and gallate-derivates. Although marketability and long-term toxicity of Galla rhois should be tested, it may be applied as a food additive to elevate food quality.

Fraxetin induces cell death in colon cancer cells via mitochondria dysfunction and enhances therapeutic effects in 5-fluorouracil resistant cells.

Fraxetin is a natural compound extracted from Fraxinus spp. and has various functions such as antibacterial, antioxidant, neuroprotective, and antifibrotic effects. Although studies have reported its anticancer properties in lung and breast cancer, little is known about colon cancer, the most frequent type of cancer. Thus, we used two colon cancer cell lines, HT29 and HCT116 cells, to investigate whether fraxetin could inhibit the capabilities acquired during tumor development. In this study, fraxetin suppressed cell viability and induced apoptotic cell death in HT29 and HCT116 cells. Furthermore, fraxetin regulated the expression of proteins involved in apoptosis in HT29 and HCT116 cells. Additionally, fraxetin induced reactive oxygen species levels and calcium influx with loss of mitochondrial membrane potential (ΔΨm) and endoplasmic reticulum stress. Moreover, fraxetin induced G2/M arrest and modulated the intracellular signaling pathway, including AKT, ERK1/2, JNK, and P38. Nevertheless, we found no cause-effect correlation between the antiproliferative action of fraxetin and modulation of the phosphorylation state of signaling proteins. Fraxetin-induced inhibitory effect on colon cancer cell viability was synergistic with 5-fluorouracil (5-FU) or irinotecan even in 5-FU resistant-HCT116 cells. Collectively, our results suggest that fraxetin can be effectively used as a therapeutic agent for targeting colon cancer, although it is necessary to further elucidate the relationship between the hallmark capabilities that fraxetin inhibits and the intracellular regulatory mechanism.

Brassinin Abundant in Brassicaceae Suppresses Melanogenesis through Dual Mechanisms of Tyrosinase Inhibition.

Brassinin is a phytoalexin abundant in plants, especially in cabbage, and has been reported to act as an anti-cancer and anti-inflammatory agent. However, limited studies are available to elucidate the functionalities of brassinin. Here, we tested the effects of brassinin on melanogenesis using cell-free and cell-based biochemical analysis and docking simulation. Cell-free experiments exhibited that brassinin has antioxidant and anti-tyrosinase activities. When applied to B16F10 cells stimulated with a melanogenesis inducer α-MSH, brassinin pretreatment significantly reduced melanin accumulation and cellular tyrosinase activity. Docking simulation indicates that the docking score of brassinin to the binding pocket of tyrosinase is better than that of kojic acid or arbutin, anti-melanogenic positive controls, indicating that brassinin inhibits melanogenesis at least partially by binding to and inactivating tyrosinase. In addition, qPCR results showed that brassinin reduced tyrosinase mRNA levels. Together, these results suggest that brassinin exerts anti-melanogenesis effects by inhibiting both the activity and mRNA expression levels of tyrosinase. Therefore, our study showed that brassinin has the potential to be used in pharmaceutical or cosmetic products for depigmentation.

The multi-functional roles of forkhead box protein O in skin aging and diseases.

Forkhead box, class O (FoxO) family members are multifunctional transcription factors that are involved in several metabolic processes, including energy metabolism, apoptosis, DNA repair, and oxidative stress. However, their roles in skin health have not been well-documented. Recent studies have indicated that FoxOs are important factors to control skin homeostasis and health. The activation or deactivation of some FoxO family members is closely related to melanogenesis, wound healing, acne, and melanoma. In this review, we have discussed the recent findings that demonstrate the relationship between FoxOs and skin health as well as the underlying mechanisms associated with their functions.

PAR2 Deficiency Induces Mitochondrial ROS Generation and Dysfunctions, Leading to the Inhibition of Adipocyte Differentiation.

Protease-activated receptor 2 (PAR2) is a member of G-protein-coupled receptors and affects ligand-modulated calcium signaling. Although PAR2 signaling promotes obesity and adipose tissue inflammation in high fat- (HF-) fed conditions, its role in adipocyte differentiation under nonobesogenic conditions needs to be elucidated. Here, we used several tissues and primary-cultured adipocytes of mice lacking PAR2 to study its role in the development of adipose tissues. C57BL/6J mice with PAR2 deficiency exhibited a mild lipodystrophy-like phenotype in a chow diet-fed condition. When adipocyte differentiation was examined using primary-cultured preadipocytes, PAR2 deficiency led to a notable decrease in adipocyte differentiation and related protein expression, and PAR2 agonist treatment elevated adipocyte differentiation. Regarding the mechanism, PAR2-deficient preadipocytes exhibited impaired mitochondrial energy consumption. Further studies indicated that calcium-related signaling pathways for mitochondrial biogenesis are disrupted in the adipose tissues of PAR2-deficient mice and PAR2-deficient preadipocytes. Also, a PAR2 antagonist elevated mitochondrial reactive oxygen species and reduced the MitoTracker fluorescent signal in preadipocytes. Our studies revealed that PAR2 is important for the development of adipose tissue under basal conditions through the regulation of mitochondrial biogenesis and adipocyte differentiation.